rs369884505
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_000719.7(CACNA1C):āc.2824A>Gā(p.Thr942Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,611,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T942S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000719.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.2824A>G | p.Thr942Ala | missense_variant | 21/47 | ENST00000399655.6 | |
CACNA1C | NM_001167623.2 | c.2824A>G | p.Thr942Ala | missense_variant | 21/47 | ENST00000399603.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.2824A>G | p.Thr942Ala | missense_variant | 21/47 | 5 | NM_001167623.2 | ||
CACNA1C | ENST00000399655.6 | c.2824A>G | p.Thr942Ala | missense_variant | 21/47 | 1 | NM_000719.7 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151626Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249212Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135202
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460238Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726506
GnomAD4 genome AF: 0.0000198 AC: 3AN: 151626Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74014
ClinVar
Submissions by phenotype
Timothy syndrome;C2678478:Brugada syndrome 3;CN260585:Long qt syndrome 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 09, 2021 | - - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 22, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 13, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at